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Circulating antibodies to guanosine in systemic lupus erythematosus: correlation with nephritis and polyserositis by acute and longitudinal analyses

Jerry L Pettis Memorial Veterans Medical Center, Research Service 151, 11201 Benton Street, Loma Linda, CA 92357, USA Keith.Colburn{at}med.va.gov; Loma Linda University School of Medicine, Department of Medicine, Division of Rheumatology, Loma Linda, California, USA

L M Green

Jerry L Pettis Memorial Veterans Medical Center, Loma Linda, California, USA; Loma Linda University School of Medicine, Department of Medicine, Division of Rheumatology, Loma Linda, California, USA; Loma Linda University, Department of Microbiology and Molecular Genetics and Physiology, Loma Linda, California, USA; Radiobiology Program, Loma Linda University, Loma Linda, California, USA

A K Wong

Veterans Medical Center-Sepulveda, Department of Medicine, Division of Rheumatology, UCLA, Sepulveda, California, USA

Systemic lupus erythematosus (SLE) is characterized by autoantibodies, including antibodies to the nucleosides of DNA. Guanosine is the most immunogenic nucleoside. In this study serum antiguanosine antibody levels were compared with disease activity, determined by their SLEDI score, in 86 patients with SLE. Sera from these patients were tested, by ELISA, for autoantibodies to guanosine, single-stranded DNA (ssDNA), and double-stranded DNA (dsDNA). Anti-doublestranded DNA levels were also measured by RIA. Resultant values from these assays were correlated with SLE disease activity, and compared with specific features of SLE. The strongest correlation was higher levels of antiguanosine antibodies in patients with active lupus nephritis and polyserositis compared to patients with inactive disease (P < 0.0001). Antiguanosine levels also correlated with arthritis (P < 0.006), CNS lupus (P < 0.005), and hematologic manifestations of SLE (P < 0.002). To test the validity of this association in chronic SLE, serum antiguanosine antibodies were measured in patients with SLE at various phases of disease activity. Twelve patients with SLE had serum samples drawn at active, active-improved, and inactive phases over a 3–7 y period. Differences were significant for serum antiguanosine antibodies in the active group compared to the inactive group (P < 0.05) and the active vs the active-improved group (P < 0.02), unlike those for dsDNA and ssDNA by ELISA or RIA. Antiguanosine antibodies correlated more closely with disease activity in SLE patients in this longitudinal study than either anti-dsDNA or ssDNA antibodies. Thus, antibodies to guanosine correlated as well or better with disease activity than the other anti-DNA antibodies measured and should be considered to contribute to the pathology of SLE, especially lupus nephritis.

Key Words: systemic lupus erythematosus (SLE) • antinuclear antibodies • autoantibodies • antiguanosine

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